Central nervous system stimulants such as d-amphetamine (AMP) and methylphenidate are known to enhance motoric outflow in animals and man. In rats, moderate doses of AMP produce enhanced locomotor activity (hyperlocomotion) and higher doses produce repetitive stereotyped responses. These CNS stimulants paradoxically reduce motoric activity in hyperactive children. AMP and non-AMP stimulants produce potent effects on brain dopamine (DA) neurons. The effects of the stimulants on DA neurons in the mid-brain (nucleus A9 and A10) are thought to be critical for the enhanced motor effects of these drugs. The ability of AMP to release DA from axon terminals of the A10 neurons projecting to the nucleus accumbens septi (NAS) has been found to be important for the AMP-induced hyperlocomotion. Low doses of the direct acting DA agonist, apomorphine (APO) produces hypolocomotion by interacting with DA autoreceptors (on the DA soma/dendritic region) which result in a reduction of DA neuronal impulse flow. Recently, it has been shown that low doses of AMP also produce hypolocomotion in some strains of mouse. Hypolocomotion only occurred in mouse strains with a high density of DA post-synaptic receptors (e.g. BALB/c) but not in those with a low density of receptors (e.g. CBA). This hypolocomotor affect of AMP mimics the situation found in hyperkinetic children. The mice with high receptor density might therefore be useful models to determine the basis of AMP's beneficial effect in hyperkinetic children. Single cell recording and microiontophoresis techniques will be used to test the hypothesis that the low doses of AMP, which produce hypolocomotion, preferentially release dendritic DA in the BALB/c (and not axon terminal DA in the NAS) to inhibit A10 neuronal impulse flow. Extracellular recording will be made from A10 DA neurons projecting to the NAS and from NAS neurons in the BALB/c and CBA strains. A dose-response curve for AMP-induced inhibition of impulse flow will be determined for both A10 and NAS neurons. Because the BALB/c has a higher midbrain DA cell density (and perhaps more dendro-dendritic DA autoreceptor interactions) than does the CBA, AMP should inhibit A10 impulse flow at a lower dose than NAS neuronal impulse flow in the BALB/c. In the CBA, it is predicted that there will be no significant difference in AMP's potency to inhibit A10 and NAS impulse flow. Proof of this hypothesis would suggest a possible mechanism by which AMP produces hypolocomotion in animals, and also provide a foundation for future experiments aimed at more fully testing this hypothesis.